Cancer is one of the leading causes of death in our country today. Despite extensive research, a cure for cancer is not yet a reality. Taxol is known to be cytotoxic against numerous malignant tumors. The results of studies indicate that taxol has been effective against breast cancer, colon cancer, skin cancer, carcinosarcoma in rats, leukemia in mice, malignant melanoma, and ovarian cancer (Hei and Hall 1993; Joyce 1993; Coghlan 1993; Guenard, Gueritte-Voegelein, and Pitier 1993).
After thirty years of research, taxol is no longer an experimental drug. In December, 1992, the Food and Drug Administration (FDA) approved taxol, also known as Paclitaxal, for general use in patients with advanced ovarian and breast cancer.
Studies show taxol to be an inhibitor of cell division. The cellular target of taxol is tubulin. Other cancer drugs prevent the assembly of tubulin into microtubules, but taxol promotes tubulin assembly and inhibits the disassembly process (Guenard, Gueritte-Voegeiein, and Pitier 1993; Richeimer, Tinnermeier, and Timmons 1992; Coghlan 1993). Taxol blocks cells at the G.sub.2 and M phases of the cell cycle (Hei and Hall 1993).
Taxol was discovered in 1963 in the bark of the Pacific yew (Taxus brevifolia), a slow-growing environmentally sensitive native tree often found in the old-growth forests (Joyce 1993; "Taxol " 1993). Taxol and similar compounds are also found in other species of yew.
If taxol therapy is approved for other types of cancer, the current taxol supply will be rapidly depleted. Each treatment requires 300 milligrams of taxol and four to ten doses are required for a total regimen. The result is an average of two grams of taxol per cancer patient. If 12,000 cancer patients are treated, 24 kilograms of taxol would be needed. It takes 30 pounds of bark to produce one gram of taxol; therefore, 60 pounds of bark are needed per cancer patient. On an average, 12.5 pounds of bark are produced per yew tree (Joyce 1993).
The separation of taxol is very difficult and requires a multi-step procedure. Yew trees produce other chemicals called taxanes that are similar in structure to taxol. FIG. 1 shows the chemical structure of taxol (Arbuck, 1993a). Structural differences between taxol and various taxanes are as follows: for baccatin, the group at C 13 is replaced with -OH; for 10-deacetyl baccatin III, the group at C 13 is replaced with -OH, and -OAc at C 10 is replaced with -OH); for cephalomannine, the two starred C's are removed to make a butyl group; for 10-deacetyl taxol, the -OAc at C 10 is replaced with -OH, and the -OH at C 7 switches from the front to the back of the structure.
The baccatin group is the most similar in structure to taxol, but without the side chain on carbon 13. Total synthesis has taken years to develop due to the complex molecular structure of taxol. Final synthesis of taxol was published in February, 1994. A semi-synthetic taxol product, Taxotere, can be made from 10-deacetyl baccatin III.
Because of the enormous demand for taxol and the limited natural supply of yew trees, scientists and researchers are trying to develop new and effective ways of producing the drug. Scientists have extracted taxol and other taxanes from yew needles, bark, tree fungus, and other species besides T. brevifolia. One of these studies found that cuttings of certain Taxus species transfer taxol into the culture medium (Hoffman and Franzen 1994). The purpose of this study was to determine whether taxol could be transferred from yew tree cuttings into a culture medium over time.